Australian Regenerative Medicine Institute, Monash University, Clayton Campus, VIC 3800, Australia.
Neuromuscul Disord. 2010 Dec;20(12):826-32. doi: 10.1016/j.nmd.2010.08.004. Epub 2010 Sep 17.
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. As in humans, zebrafish dystrophin is initially expressed at the peripheral ends of the myofibres adjacent to the myotendinous junction and gradually shifts to non-junctional sites. Dystrophin-deficient zebrafish larvae are characterised by abundant necrotic fibres being replaced by mono-nucleated infiltrates, extensive fibrosis accompanied by inflammation, and a broader variation in muscle fibre cross-sectional areas. Muscle progenitor proliferation cannot compensate for the extensive skeletal muscle loss. Live imaging of dystrophin-deficient zebrafish larvae documents detaching myofibres elicited by muscle contraction. Correspondingly, the progressive phenotype of dystrophin-deficient zebrafish resembles many aspects of the human disease, suggesting that specific advantages of the zebrafish model system, such as the ability to undertake in vivo drug screens and real time analysis of muscle fibre loss, could be used to make novel insights relevant to understanding and treating the pathological basis of dystrophin-deficient muscular dystrophy.
杜氏肌营养不良症是由肌营养不良蛋白基因突变引起的。与人类一样，斑马鱼肌营养不良蛋白最初在靠近肌节连接处的肌纤维的外周末端表达，然后逐渐转移到非连接位点。肌营养不良蛋白缺失的斑马鱼幼虫的特征是大量坏死纤维被单核细胞浸润所取代，广泛的纤维化伴有炎症，以及肌纤维横截面积的更大变化。肌肉祖细胞的增殖不能补偿广泛的骨骼肌损失。肌营养不良蛋白缺失的斑马鱼幼虫的活体成像记录了肌肉收缩引起的肌纤维分离。相应地，肌营养不良蛋白缺失的斑马鱼的进行性表型类似于人类疾病的许多方面，这表明斑马鱼模型系统的特定优势，如进行体内药物筛选和实时分析肌纤维损失的能力，可以用于深入了解和治疗肌营养不良蛋白缺失性肌营养不良症的病理基础。
